Circadian rhythm of cytokine secretion following thermal injury in mice: implications for burn and trauma research.

Although there are many reports of circadian variation in hormone secretion, there are only a few reports on the relationship between circadian rhythm and cytokine production. The aim of the present studies was to investigate whether there is a circadian effect on cytokine production of splenic lymphocytes and adherent splenocytes in mice after burn or sham injury. We selected day 7 after injury for our determinations because we have previously shown day 7 is the time of maximal suppression of T cell IL-2 and IFNgamma production and maximal increase in adherent cell proinflammatory cytokine secretion in this model.

Injury induces deficient interleukin-12 production, but interleukin-12 therapy after injury restores resistance to infection.

Objective: To assess at serial intervals the production of interleukin-12 (IL-12) by monocytes/macrophages from the peripheral blood of injured patients and control subjects, and using a mouse model to confirm human findings and explore the effectiveness of low-dose IL-12 therapy in restoring resistance to infection after injury.

Summary Background Data: Serious injury is associated with loss of function of the T helper 1 lymphocyte phenotype, but little is known about IL-12 production in injured patients. The authors previously reported that early, moderate-dose IL-12 therapy in a mouse model of burn injury restored resistance to a later infectious challenge (cecal ligation and puncture, CLP).

Decreased interleukin-2 production in murine acute pancreatitis: potential for immunomodulation.

Background & Aims: The role of the cytokine interleukin 2 (IL-2) has long been recognized as central to normal immunologic function and defense against infection after burns and trauma, but little effort has been directed towards its role in acute pancreatitis (AP), which also has a high mortality related to sepsis. This study investigated the potential role of IL-2 in mice with diet-induced AP.

Methods: AP was induced in mice by 10 days of feeding a choline-deficient, ethionine-supplemented diet.

Long-term immunotherapeutic intervention with pentoxifylline in a mouse model of thermal injury and infection.

Major thermal or traumatic injury often results in abnormalities of immune function, and these abnormalities contribute to the increased susceptibility to infection observed in these patients. Abnormalities of T-cell function, including decreased proliferation and secretion of cytokines are observed following major injury and, conversely, there is markedly increased monokine production. Thus, therapy of this syndrome might logically be aimed at modulating the immune system to upregulate T-cell function and downregulate monocyte hyperactivation.

Molecular mechanisms of decreased interleukin-2 production after thermal injury.

Background: Among the fundamental immunologic abnormalities induced by serious traumatic or thermal injury are alterations in T cell activation, reduced lymphocyte interleukin-2 (IL-2) production, and associated depression of T lymphocyte proliferation. This study attempts to localize the cellular mechanisms underlying abnormal IL-2 production in thermal injury.

Methods: Following National Institutes of Health guidelines, 150 A/J mice were anesthetized, subjected to a 20% full-thickness scald burn injury or sham burn, and killed at intervals from 4 to 21 days later; splenocytes were harvested for in vitro studies.